Vaccine targeting KRAS in pancreatic and colorectal cancer shows promise

A new vaccine shows encouraging early results as a potential off-the-shelf treatment for certain patients with pancreatic or colorectal cancer, according to a study co-led by researchers at Memorial Sloan Kettering Cancer Center (MSK). The vaccine targets tumors with mutations (or changes) in the KRAS gene, a driving force in many cancers.

This cancer vaccine is different from another type of pancreatic cancer vaccine, which is custom-made for each patient using messenger RNA (mRNA). Both are therapeutic vaccines given after surgery to prevent or delay the cancer from coming back in high-risk patients.

“Having a vaccine that’s ‘off-the-shelf’ would make it easier, faster, and less expensive to treat a larger number of patients,” says medical oncologist and pancreatic cancer specialist Eileen O’Reilly, MD, who helped lead the trial and is one of the corresponding authors in the study published in Nature Medicine. “This gives hope for people with pancreatic and colorectal cancer who have been out of effective treatments when their disease returns.”

Dr. O’Reilly is co-corresponding author of the Nature Medicine study, along with Shubham Pant, MD, of MD Anderson Cancer Center, and Christopher M. Haqq, MD, PhD, of Elicio Therapeutics.

Clinical Trial Results for Pancreatic and Colorectal Cancer KRAS Vaccine

The phase 1 trial involved 25 patients whose pancreatic or colorectal cancer had certain KRAS mutations and were at high risk of the cancer returning after surgery. The results demonstrated this vaccine is safe and appears to stimulate the patient’s immune system to create cancer-fighting cells:

• 84% of patients had the desired immune response, meaning that immune T cells targeting KRAS-mutated cancer cells were activated and grew in number.
• Also in 84% of patients, a marker for lingering cancer cells — the amount of tumor DNA circulating in the blood — was reduced. In 24% of patients, the tumor DNA was completely absent.
• Perhaps most significant, patients who had a higher T cell response also experienced a longer time without the disease returning, known as relapse-free survival.

“In patients whose immune system appeared to respond to the vaccine, the recurrence of cancer was delayed compared with patients who did not respond to the vaccine,” Dr. O’Reilly says. “That’s the type of early clinical effect we can build on.”

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How Off-the-Shelf Vaccines Targeting KRAS Mutations Differ From Personalized mRNA Vaccines

A different approach to activating immune cells has been led by surgical oncologist Vinod Balachandran, MD. He is investigating whether a personalized mRNA vaccine using proteins from a patient’s pancreatic tumors will alert their immune system that the cancer cells are foreign. In this way, the mRNA vaccine trains the body to protect itself against cancer cells. This vaccine is now being tested in a phase 2 research study at MSK and other institutions.

Personalized vaccines — while promising — also have challenges. They take time to make and are costly. By contrast, an off-the-shelf vaccine manufactured in batches could be given to patients with minimal delay and would be cheaper to produce.

“These findings are exciting because they show we may have more than one way to activate immune cells to target pancreatic cancer,” Dr. O’Reilly says.